The subject of the invention is the use of protein material whose rate of digestion has been reduced, for the preparation of a composition which makes it possible to modulate the postprandial plasma amino acid level. The subject of the invention is also a composition intended to be administered by the enteral route to a mammal containing a protein material whose rate of digestion has been slowed down.
Because of a constant need for nutrients and the periodic nature of the diet in humans, the body has had to develop processes for storing the nutrients consumed in excess during meals and mechanisms for mobilizing these reserves during the period of physiological starving. The alternation of periods of food consumption and of starving are responsible for profound modifications in the various pathways for the metabolism of nutrients.
These nychthemeral variations affect the synthesis and the degradation of proteins and consequently the protein balance. Thus, the negative protein balance during the period of physiological starving becomes positive during the postprandial period, a phase for assimilating nutrients from the digestive tract. The relative importance of each phase then determines the variation in the body protein mass. It is therefore essential to be able to improve the postprandial protein gain in order to optimize the variation in the protein mass.
The ingestion of meals consisting of proteins causes an increase in the plasma amino acid level. This rise in the availability of amino acids is associated with a rearrangement of the various components of protein metabolism (protein degradation, protein synthesis, amino acid oxidation). Recently, Boirie et al. (Proc. Natl. Acad. Sci. USA, 94, 14930-14935, 1997) have shown in young healthy volunteers that the postprandial protein gain depended on the rate of digestion of the ingested proteins (period between ingestion and absorption of the nutrients by the body).
Some proteins with a fast rate of digestion, such as whey proteins, can have a high nutritive value, that is to say an adequate and balanced supply of amino acids which are essential for the human body, such as valine, leucine, isoleucine, phenylalanine, lysine, methionine, tryptophan and threonine. However, in spite of this good amino acid balance, the body""s use of the amino acids derived from these proteins is not optimum, since they are digested too rapidly. Also, document WO 97/05785 describes a composition used in foods for newborns which contains slow-digesting proteins, said proteins having been modified beforehand so as to slow down the rate of digestion.
Other sources can therefore be used which contain proteins having a naturally slower rate of digestion, such as caseins, for example, but whose amino acids supply and balance are not optimum.
The present invention aims to provide for the nutritional needs of certain categories of people by means of proteins whose rate of digestion is reduced.
The invention thus relates to the use of a slow-digesting protein material for the preparation of a composition intended to be administered enterally to a mammal so as to modulate the postprandial plasma amino acid level, said protein material having been previously treated so as to convert the fast-digesting proteins which it contains to slow-digesting proteins, characterized in that the slow-digesting protein material is a material containing microparticulate gelled proteins combined with polysaccharides under conditions of thermodynamic incompatibility.
To date, it has never been proposed to reduce the rate of digestion of a protein with the aim of modulating the postprandial plasma amino acid level so as to: a) increase the postprandial protein gain; and/or b) avoid a metabolic overloading of certain organs and/or certain enzymes, and/or c) limit daily food intake by virtue of a satiating effect of these proteins, and/or d) compensate for certain dysfunctions in the metabolism of amino acids and more specifically for enzymatic deficiencies, e) improve the regeneration of tissues, in particular the processes of wound healing.
This treatment is particularly advantageous for proteins of high nutritional value which are digested too rapidly, this being so as to optimize the protein gain.
The subject of the invention is also a composition intended to be administered enterally to a mammal, containing a slow-digesting protein material which has been treated beforehand so as to convert the fast-digesting proteins which it contained to slow-digesting proteins, characterized in that the slow-digesting protein material is a material containing microparticulate gelled proteins combined with polysaccharides under conditions of thermodynamic incompatibility.
The compositions thus obtained may be particularly suitable for: minimizing the losses of body proteins in elderly persons, patients who are seriouly ill and people on a low-calorie diet; patients suffering from renal or hepatic disorders; patients suffering from disfunctions in the metabolism of amino acids such as, for example, hyperphenylalaninemia or other aminoacidopathies; patients treated with L-DOPA; and premature babies.
They may also be intended for the nutrition of pets, in particular that of elderly subjects, the young during the period of growth and for controlling the body weight of some subjects.
In the context of the present invention, a slow-digesting protein material is a material which, when provided in the form of a solution and digested by 140-200 g rats, leads to a disappearance of half of the ingested nitrogen present in the digestive tract in more than 80 min.
Fast protein refers to proteins which, when they are ingested in the form of a solution by 140-200 g rats, leads to a disappearance of half of the ingested nitrogen present in the digestive tract in less than 70 min.
To carry out the present invention, a protein material, that is to say any material comprising proteins, whether they are of animal, plant or microbial origin, in particular proteins of milk, oil-producing plants, leguminous plants, egg or brewery yeasts, for example is used.
The materials containing proteins having a high nutritive value, based on the recommended intakes, are particularly indicated in the context of the present invention. These proteins may contain a balanced and high content of each of the amino acids essential for the body, such as lysine, tryptophan, leucine, isoleucine, valine, phenylalanine, methionine and threonine, for example.
Preferably, the protein-containing material (untreated) comprises fast-digesting proteins, such as for example whey proteins.
The protein-containing material is treated so that the rate of digestion of said proteins is slowed down. To this effect, the protein-containing material is mixed with polysaccharides and, under conditions of thermodynamic incompatibility, form microparticles which are gelled by heat treatment.
Indeed, biopolymers such as proteins and polysaccharides may exhibit thermodynamic incompatibility; that is to say that above a threshold concentration, they do not form a homogeneous mixture and separate spontaneously into two phases. One is enriched in proteins, the other is enriched in polysaccharides. At this initial stage, the separation of the two phases is achieved by formation of microscopic droplets, which may be gelled; in the case of protein droplets, a heat treatment often makes it possible to form a gel. Thus, the protein microparticle formation results from a phase separation and a spontaneous gelling of an aqueous mixture of proteins and polysaccharides (Syrbe, PhD Thesis, Techn. Univ. Munich, 1997).
The polysaccharides according to the present invention may be chosen in particular from alginates, xanthan gum, gum arabic, guar, starch, maltodextrins and dextrins, pectins, kappa-carrageenans, iota-carrageenans, lambda-carrageenans, methyl cellulose and carboxymethyl cellulose, sulfated dextrans and/or gellan gum.
The concentration of proteins and polysaccharides in the mixture may be respectively between 3 and 12% and between 0.2 and 1%. The protein/polysaccharide ratio may thus vary from 3:1 to 24:1.
The microparticles may for example be prepared from a mixture of a solution of alginate and a solution of serum proteins. The solution of alginate is preferably at 3% and pH 7 and the solution of serum proteins at 15%, pH 6.6. The mixture may thus be heated at a temperature of between 70 and 130xc2x0 C. for a period of 1-60 minutes.
The microparticles obtained have a diameter preferably of between 200 nm and 100 microns.
The conditions for treating the protein-containing material must be preferably chosen so as to achieve a level of slowing down of the rate of digestion of said proteins such that when the treated protein material is orally administered in the form of a solution to 140-200 g rats, it leads to a disappearance of half of the ingested nitrogen present in the digestive tract in more than 80 min, for example.
The protein material thus treated may be advantageously used for the preparation of a food or pharmaceutical composition intended to be orally administered to a mammal so as to: 1) increase the postprandial protein gain, and/or 2) avoid a metabolic overloading of certain organs and/or certain enzymes, and/or 3) limit daily food intake by virtue of a satiating effect of these proteins, and/or 4) compensate for certain dysfunctions in the metabolism of amino acids and more specifically for enzymatic deficiencies, and/or 5) improve the efficacy of treatments with L-DOPA, 6) improve the regeneration of tissues, in particular the processes of wound healing.
The present use is however not limited to a protein material treated as described above. Indeed, other treatments may also induce a reduction in the rate of digestion of a protein-containing material. The present use is therefore intended to also use any protein material which has been treated beforehand so as to convert the fast-digesting proteins which it contained to slow-digesting proteins.
Thus, certain technological modifications, such as the thermal gelling, the mixing of these proteins with polysaccharides which can gel in the stomach, the formation of gelled microparticles as well as the preliminary supply of casomorphines in the form of a casein hydrolysate can make the rate of digestion of proteins slower.
It is possible, for example, to use one of the materials containing proteins which is cited above, combined with anionic polysaccharides.
The slow-digesting protein material is capable of improving or preventing problems linked with various physiological or physiopathological states. Indeed, the protein materials with a slow rate of digestion can act according to 4 principal modalities: by optimizing the postprandial protein gain, by avoiding excessive functioning for key organs or for certain enzymes, by optimizing treatments with L-DOPA and by increasing the sensation of satiety. The conditions governing the use of these proteins will depend in particular on the categories of people concerned.
In the context of the optimization of the postprandial protein gain, cases of undernourishment may be treated. Undernourishment frequently exists in elderly subjects or during diseases which comprise a substantial loss of body proteinsxe2x80x94renal insufficiency, severe burns, trauma, surgical or infectious stress, inflammation, cancer or AIDS. This metabolic state manifests itself by a negative nitrogen balance which is the consequence of a fusion of the body, and more particularly muscle, proteins. Indeed, the muscle proteins are degraded so as to provide energy to the body and allow the redistribution of the amino acids to the synthesis of specific proteins.
In cases of undernourishment, the ingestion of slow-digesting protein material is capable of limiting this protein loss, by optimizing the postprandial protein gain. This protein material ought to increase the rate of physiological recovery, resistance to attacks, the quality of life and therefore the vital prognosis.
Renal abnormality, in the broad sense of the term, is an example of the use of the slow-digesting protein material which is not solely based on the optimization of the postprandial protein gain, although it is an essential component thereof. Indeed, during renal abnormalities, patients are subjected to a strict hypoprotein diet so as to reduce the production of nitrogenous waste. It is commonly accepted that such a diet has a favorable effect on the general condition, the quality of life and even on the renal function. However, this diet is very poorly tolerated by patients. The ingestion of slow-digesting protein material contributes toward:
1) reducing the production of nitrogen which should be subsequently eliminated by the kidneys;
2) distributing this production over a much longer period; and
3) increasing the satiating action of this type of protein in order to ensure better tolerance of the diet. Proteins with a slow rate of digestion are consequently particularly suitable for the nutrition of patients with renal disorders.
Likewise, the slow-digesting protein material may be prescribed for patients with pathological hepatic conditions. After a meal composed of various nitrogenous compounds (proteins, peptides, amino acids), the liver will try to maintain the amino acid concentration within physiological limits by breaking down a portion of the amino acids derived from the diet. A moderate arrival of dietary amino acids is capable of reducing the excessive activity of an organ which exhibits pathological conditions and which will consequently make it possible to avoid excessive work. In addition, the slow-digesting protein material induces a better postprandial protein gain.
During a deficiency in proteolytic pancreatic enzymes, the ingestion of slow-digesting protein material can contribute toward improving the digestion process. This benefit is brought about by the reduction in the quantity of substrate to be hydrolyzed by the proteolytic enzymes of the pancreas and therefore by the obtaining of a better enzyme/substrate ratio. Furthermore, with the slow-digesting protein material, there is a better postprandial protein gain.
In diseases where dysfunctions exist in the metabolism of amino acids and more specifically enzyme deficiencies in the pathway of degradation of these amino acids (phenylalaninemia and phenylketonuria, hypertyrosinemia, histidinemia, homocystinuria, amino acidopathies linked to branched amino acids, for example), the accumulation of these amino acids or of one of their degradation products produces neurological and clinical complications. To avoid this accumulation, a dietetic treatment is prescribed. It consists of a diet which does not containxe2x80x94or contains a very small quantity ofxe2x80x94the amino acid implicated in the development of the disease. The specific products developed for these populations are composed either of free amino acids, or of highly hydrolyzed proteins. However, these mixtures do not possess a pleasant taste. Furthermore, to avoid diarrhea following on from the hyperosmolarity of the products, consumers should ingest the products in the form of small meals. The protein material which possesses both a slow rate of digestion and a small content of the implicated amino acid, makes it possible to improve the taste and therefore the tolerance of the diet, to limit the risk of diarrhea, to avoid plasma fluctuations in amino acids, and to increase the postprandial protein gain.
The use of slow-digesting protein material can also be envisaged for people who are not undernourished, such as premature babies, newborns, children, obese individuals and elderly persons, for example.
The ingestion of slow-digesting protein material, in premature babies, newborns or children who are not undernourished, by providing a better yield of use of the dietary proteins, is capable of promoting body growth.
The slow-digesting protein material, by reducing the food intake by a satiating mechanism, may be administered to people with disorders of weight homeostatis (obesity) or during episodes of bulimia. It can limit the reduction in the protein mass subsequent to being on a low-caloric diet. These two combined factors make it possible to reduce their fatty mass with, on the one hand, greater ease for reducing their supplies and, on the other hand, a better preservation of their protein mass.
In elderly persons, compared with young subjects, there is a reduction in the body protein mass, a reduction which has an influence on the autonomy, the resistance to attacks (diseases, various stresses) and the ability to recover from these attacks. Furthermore, aging is associated with a reduction in renal activity. The slow-digesting protein material, by therefore allowing better preservation of the protein mass, thus makes it possible to avoid renal excesses.
The protein material with a slowed rate of digestion, by providing the amino acids in a more continuous and regular manner, makes it possible to promote the synthesis of novel tissue materials which are involved in the processes of wound healing or of regeneration of biological tissues.
The protein material with a slowed rate of digestion may be intended for the nutrition of pets, in particular that of elderly subjects and the young in the growth phase. It can also be administered to certain subjects so as to control their body weight.
The proteins contained in the compositions according to the invention can provide from 5 to 100% of the total energy, in particular from 8 to 30%, and preferably from 10 to 20%. In the case of the compositions intended for use as pet food, the protein content may be up to 40% on the basis of the dry extract.
These compositions preferably comprise a source of carbohydrates providing 0 to 70% of the total energy. The carbohydrates are important nutrients for re-establishing the energy balance. All carbohydrates can be used, in particular maltodextrins, sucrose, lactose and glucose, for example.
The compositions may comprise a source of lipids which provide up to 35% of the total energy. Vegetable oils are recommended, in particular those of soybean, oil palm, coconut, sunflower and the like. In the case of the compositions intended for use as pet food, the source of lipids can provide up to 60% of the total energy.
The energy value of these compositions may be between 70 and 200 Kcal/100 ml, for example.
In the case of the compositions intended for infant nutrition, the proteins preferably represent 0.45 to 0.7 g/100 kJ, the carbohydrates preferably 1.7-3.4 g/100 kJ and the lipids preferably 0.1-1.5 g/100 kJ.
In the case of compositions intended for patients suffering from phenylketonurea, the protein material may contain about 50% of caseinoglycomacropeptides, a source of carbohydrates, a source of lipids and vitamins and minerals.
The compositions according to the present invention may be prepared in all sorts of ways, the steps of manufacture generally including a dispersion of the ingredients in water, emulsification and pasteurization.
The compositions may be prepared in the form of liquid or semisolid concentrates or drinks or in the form of a powder which may be reconstituted in water, for example. They may also be provided in a solid form, such as cereals, nutritional bars, for example.
Minerals, vitamins, salts, emulsifiers or flavoring compounds may also be added to the compositions, as required. The vitamins and minerals may represent from 25 to 250% of the recommended daily supplies. In the case of infant formulas, the quantities of vitamins and minerals prescribed by the European Directive are added.